Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis

He Li, Lihui Xie, Lei Zhu, Zhaohuai Li, Rong Wang, Xiuxing Liu, Zhaohao Huang, Binyao Chen, Yuehan Gao, Lai Wei, Chang He, Rong Ju, Yizhi Liu, Xialin Liu (), Yingfeng Zheng () and Wenru Su ()
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He Li: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Lihui Xie: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Lei Zhu: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Zhaohuai Li: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Rong Wang: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Xiuxing Liu: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Zhaohao Huang: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Binyao Chen: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Yuehan Gao: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Lai Wei: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Chang He: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Rong Ju: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Yizhi Liu: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Xialin Liu: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Yingfeng Zheng: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science
Wenru Su: Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Uveitis is a severe autoimmune disease, and a common cause of blindness; however, its individual cellular dynamics and pathogenic mechanism remain poorly understood. Herein, by performing single-cell RNA sequencing (scRNA-seq) on experimental autoimmune uveitis (EAU), we identify disease-associated alterations in cell composition and transcriptional regulation as the disease progressed, as well as a disease-related molecule, PIM1. Inhibiting PIM1 reduces the Th17 cell proportion and increases the Treg cell proportion, likely due to regulation of PIM1 to the protein kinase B (AKT)/Forkhead box O1 (FOXO1) pathway. Moreover, inhibiting PIM1 reduces Th17 cell pathogenicity and reduces plasma cell differentiation. Importantly, the upregulation of PIM1 in CD4+ T cells and plasma cells is conserved in a human uveitis, Vogt-Koyanagi-Harada disease (VKH), and inhibition of PIM1 reduces CD4+ T and B cell expansion. Collectively, a dynamic immune cellular atlas during uveitis is developed and implicate that PIM1 may be a potential therapeutic target for VKH.

Date: 2022
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DOI: 10.1038/s41467-022-33502-7

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